The goal of this research is to determine whether indirect immunofluorescence and immunoperoxidase procedures with monoclonal antibodies developed against human melanoma antigens can localize tumor associated antigens (TAAs) in cryostat and conventional paraffin sections of tumor specimens. Mouse monoclonal antibodies (MAbs) have been developed against TAA from the spent medium of the M14 CDM/COH human malignant melanoma cell line which is propagated in serum-free medium. Preliminary results with one of the MAb, F11, against cell lines and cryostat sections suggested melanoma-carcinoma associated antigen (MCAA) specificity. Subsequent testing of the F11 MAb against a spectrum of 60 cryostat and 30 paraffin sections of various histological types support the MCAA-specificity of the F11 MAb. In addition, the reaction of the F11 MAb with 1/5 (20%) fetal paraffin sections suggest that the MCAA is an oncofetal antigen. Additionally, by a competitive enzyme-linked immunosorbent assay (ELISA) a statistically significant higher incidence of MCAA was detected by the F11 MAb in melanoma and carcinoma patients' sera than in sarcoma patients' or normal donors' sera (p,0.05).